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Microglia Development

Microglia are the first glial cells to be present in the brain. They arise from the endoderm-derived yolk sac, in contrast to the other neural cell types, which originate from the ectoderm. Beginning around embryonic day (E) 8, yolk sac CD45- CD117/c-kit+ erythromyeloid progenitors differentiate into CD45+ CD117/c-kitlo CX3CR1- precursors, termed A1 cells, and then subsequently develop into CD45+ CD117/c-kit- CX3CR1+ F4/80high A2 cells. Development of microglia precursor cells is dependent on a number of factors including the transcription factors PU.1/Spi-1, IRF8, and RUNX1/CBFA2, as well as IL-34 signaling through M-CSF R/CD115.

At approximately E9.5, A2 cells enter the brain rudiment via the developing circulatory system. With the aid of factors such as Matrix Metalloproteinase 8 (MMP8), MMP9, CCL2/MCP-1, IL-34, M-CSF, and Vascular Endothelial Growth Factor (VEGF), A2 cells surround the neuroepithelium of the developing brain and begin to invade the central nervous system (CNS) parenchyma by crossing the ventricular lining and pia, or at a later phase, breaching the blood vessel wall. These microglia precursor cells then migrate throughout the tissue to reach their final destinations while proliferating profusely in order to achieve a sufficient population size to meet the needs of the growing brain. Within the CNS, A2 cells continue to mature. Environmental cues drive the maturing microglia precursor cells through three distinct temporal stages that can be distinguished by specific transcriptional signatures and distinct morphologies: early microglia (E10.5 – E14), pre-microglia (E14 – postnatal day [P] 9), adult microglia (P28 and on).

R&D Systems offers a range of research tools needed for the investigation of microglia development.